The Cure for Attention Deficit Disorder was Right Under Your Nose! -An argument supporting a dietary solution for Attention Deficit Disorder By: Elizabeth Huser

Attention Deficit Disorder Defined: “a persistent pattern of inattention and/or hyperactivity-impulsivity that is more frequent and severe than is typically observed in individuals at a comparable level of development” - American Psychiatric Association Staff

Diagnosing Attention Deficit Disorder: In order to be deemed pathological by the diagnosing physician: Symptoms must appear before age 7 Symptoms must persist for at least 6 months Symptoms must appear in two settings: Work School Home An ADD diagnosis is empiricle there is no objective confirmation available from laboratory measures at this point. The diagnosis is made by a doctor based on a highly detailed clinical history, as synthesized from info provided by parents, teachers, and the affected individual. Once the basic ADHD diagnosis is established, three subtypes can be differentiated: 1. ADHD combined: type (both inattention and hyperactivity/impulsivity 2: ADHD predominately inattentive type: only inattention criteria are met 3. ADHD predominately hyperactive/impulsive type: only these criteria are met

ADD is not simply an inability to sit still… 1/2 of those with ADD during adolescence have ADD into adulthood Emotional, Social, and Family Problems Depressed Academic and Professional Performance 50% of children diagnosed ADD exhibit other psychiatric disorders later in life Higher risk for delinquency and substance abuse It’s not just a childhood disorder. For many people it persists into adulthood. The primary difficulties of impulsiveness and inattention are magnified in relationships and affect a person’s performance at work or school which definitely impacts self-esteem. Children diagnosed with attention deficit disorder are considered to be at high risk for developing other mental disorders, such as personality disorders, later on, especially if ADD is not properly attended to. Infact, ADHD constitutes one of the strongest risk factors known for mental illnesses in early adult life. The link to substance abuse and delinquency is rooted in the proneness to repeat accidents that is associated with the disorder.

Many are affected… 1993: 2 million people diagnosed ADD 2000: ADD was responsible for 30-50% of mental health service referrals for children 2000: 4 million people diagnosed ADD 2004: 2-6% of school-age children diagnosed ADD This chart shows the large increase in stimulant prescriptions between 1991-2000; this implies that ADD diagnoses are increasing. Currently more than 4 million people in the US are diagnosed ADD. Since so many people are deeply affected by this disorder, and the number continues to grow, it is imperative that safe and effective interventions are used for treatment.

International Classification of Disease Revised Edition: ADD is a neurological impairment which is categorized as a “metabolic encephalopathy” that affects the release and homeostasis of neurotransmitters. Therefore it is internationally accepted that ADD is organically expressed in the brain. However, its exact pathological nature remains obscure.

The Brain in ADD Brain activity Without ADHD Brain activity With ADHD Modern advances in neuroimaging have allowed researchers to visualize the anatomical and physiological differences in the brains of those with ADD. Volumetric analyses of brain regions have been accomplished mainly through MRI, and dynamic neuroimaging techniques such as the PET scan have allowed researchers to add a physiological dimension to the anatomical illustration. For example, using PET data, in 1990 Zametkin found that in adults diagnosed with ADHD, the brain areas that control attention use less glucose and appear to be less active, suggesting that a lower level of activity in some parts of the brain may cause inattention. The image on the left illustrates areas of activity in the brain of a person without ADHD. The image on the right illustrates the areas of activity of the brain of someone with The ADHD brain exhibits less activity in areas that control Attention according to Dr. Alan Zametkin

PET data applied to ADD Pathology In 1993 Zametkin et al. found a negative correlation between frontal lobe brain activity and symptom severity in 10 ADHD adolescents Later in 1993, the Zametkin et al. supplemented their previous conclusions with the findings that there is an inverse relationship between symptom severity in ADHD subjects and reduced metabolic rates in areas including the left anterior frontal area. This implies that inactivity in these brain regions is directly related to the symptoms ADHD patients experience. However, there is some controversy over the research by Dr. Alan Zametkin that produced these images.

Frontostriatal circuitry and possibly intracortical connections via the corpus callosum are responsible for the neuropsychological deficits associated with ADD The findings of neuroimaging studies are inconsistant, but overall they point to these main regions to be the root of ADD pathology. These regions are correlated with dopamine pathways and other aminergic systems.

The neuro-anatomical quirks from brain imaging studies are in regions essential to dopamine production Spontaneously hypertensive rats act as models for humans with ADHD. Russell et al. found depressed dopamine released in the male SHR brain, most notably in the prefrontal cortex, a brain area found to be less active in ADHD subjects in one of Zametkin’s studies. Low-dopamine levels are thought to cause the symptomatology associated with ADD. This is congruent with the action of the stimulants used to treat ADD. The abnormal neuroanatomy has not been proven to be pathological Currently, hypo-efficient dopamine systems seem to be the essence of ADD pathology

Treatment with Pharmaceuticals First line of stimulants commonly prescribed include methylphenidates such as: - Ritalin - Amphetamines - Adderall -Dexedrine Western medicine currently attributes ADD to an organic cause that is of an idiopathic nautre, and thus the medically-accepted treatment for this disorder is “palliative, symptom management with medications. In the year 2000 there were already between 1.5 and 3 million ADHD children taking methylphenidates

Stimulants Restore Normal Brain Activity Medication increases brain activity in areas lacking, particularly the frontal lobe. While each drug is different mechanistically, collectively stimulants enhance catecholamine neurotransmission, thus reversing the neurological impairment responsible for the symptoms of ADD. The effects are only temporary, but 70% of children treated with pscyhostimulants respond with decreased primary ADHD symptom severity http://www.brain-dynamics.net/research/clin_files/clin_images/adhd_spam.jpg

Low dopamine causes inattention and hyperactivity which collectively are referred to as Attention Deficit Disorder

Etiology of ADD Neurodevelopmental damage from Environmental and Heavy metal Toxicity as well has genetic flaws Are thought to cause ADD

Genetic Predisposition Familial incidence of ADD is common Characteristic polymorphisms of dopamine-related genes in individuals with ADD COMT is an enzyme that degrades dopamine Valine is an allele for the COMT gene that confers higher catabolic activity of the enzyme - less dopamine availability. Egan et al. reported a correlation between the valine/valine genotype and depressed dorsolateral prefrontal cortex activity Low dopamine may also be due to: Impaired vesicular storage of dopamine Inadequate dopamine synthesis Inadequate dopamine release Therefore, current research supports a polygenic mode of inheritance

Studies support other risk factor categories Food and additive allergies Low protein/high carbohydrate Mineral imbalances Essential fatty acid and phospholipid deficiencies Thyroid disorders B-vitamin deficiencies Phytonutrient deficiencies Amino Acid deficiencies These biochemical states are all commonly found in people who suffer from ADD. This supports the theory that the defining physiological and anatomical brain abnormalities in those afflicted by ADD may result from genetic vulnerabilities to these risk factors. Furthermore, all of these biochemical states are physiologically correlated with lowered catecholamine levels.

Combining it all…

People with ADD may be genetically predisposed to amino acid deficiency Bornstein et al. reported that 28 ADD subjects had significantly lower levels of phenylalanine, tyrosine, tryptophan, histidine, and isoleucine than the 20 control subjects

Amino Acid deficiency is clearly consistent with the pathology of ADD Tyrosine Hydroxylase is the rate limiting step in Dopamine synthesis. Since norepinephrine and epinephrine inhibit tyrosine hydroxylase, pharmacologically modulating one neurotransmitter may affect levels of other neurotransmitters Dopamine and norepinephrine are synthesized from either phenylalanine or tyrosine Tryptophan is a substrate for serotonin

Without sufficient precursor levels, neurotransmitter production is severely limited

Amino Acid Supplementation Augments Neurotransmitter levels and alleviates ADD symptoms Theanine administration was accompanied by significant increases in serotonin and dopamine concentrations without apparent initial deficiency (Yokogoshi et al. 1998) L-tyrosine supplementation resulted in increased levels of both central dopamine and norepinephrine in rats (McConnell 1985) 2-week, double-blind crossover study of DL-Phenylalanine vs. Placebo in 19 ADD patients Mean global rating of improvement in experimental subjects approached significance as compared with the control group (Wood et al. 1985) The rate-limiting enzymes for many neurotransmitter-producing pathways are normally unsaturated, therefore increased supplementation continues to show a dose-dependent relationship with neurotransmitter production. This is exemplified by the first study in which the animals were not initally deficient in theanine before adminsitration and still showed increased levels of neurotransmitters. All three studies show that amino acid supplementation is an effective means for augmenting the neurotransmitter levels associated with attention deficit disorder symptomatology.

Long Term Effects of Amphetamines? The mechanistic action and chemical structure of stimulants used for ADD treatment and illegal recreational stimulants are extremely similar. Thus, stimulants used for ADD symptom management are extremely addictive. They are a Schedule II controlled substance in the United States. Physician’s Desk Reference: “Sufficient data on saftey and efficacy of long-term use of methylphenidate in children are not yet available…” With the limited knowledge of the potential dangers of stimulant therapy, it is logical to rule out these other biological risk factors prior to subjecting a child to pharmaceutical treatment